The Roswell Park Cancer Institute (RPCI) has been continuously recognized as a Comprehensive Cancer Center since the NCI designation of such centers in 1974 and is now requesting continued federal support for the next five years. A free-standing research, education and clinical cancer care Institute, RPCI occupies a 27 acre campus near downtown Buffalo and has expanded to nearly 1.6M gsf of clinical and research space, a 16% increase since the last review period. RPCI serves a population base of ~1.5M in Western New York where the RPCI tumor registry is recording more than 3,400 new cancer patients per year. RPCI has strong collaborations with the University of Buffalo and the Hauptman-Woodward Institute for Structural Biology, but is a fully independent entity with Dr. Donald Trump, CCSG PI and RPCI President/CEO, answering only to the RPCI Board of Directors. Since the last competitive renewal, the RPCI has grown significantly as demonstrated by: 1) the recruitment of over 100 new faculty clinicians and researchers of which 43 are new CCSG members; 2) a 74% increase in total NCI funding and a 44% increase in total peer-reviewed funding; 3) a 73% increase in accrual to investigator-initiated, interventional clinical trials and a 44% increase to accrual in all interventional trials; 4) the addition of 4 new shared resources with an institutional investment of over $2.0 M and (5) the opening of a new, 177,000 gsf, state-of-the-art research building housing Program member laboratories and Shared Resources. With the growth in faculty has also come the recruitment of three Senior Leaders. In addition, a director for the newly created RPCI Office of Cancer Health Disparities Research has also been recruited. As part of the scientific growth within RPCI, a new disease-specific Research Program, the Prostate Program, has been added in this renewal bringing RPCI to a total of six Scientific Programs that also include Cancer Prevention & Population Sciences, Cell Stress & Biophysical Therapies, Genetics, Molecular Targets & Experimental Therapeutics and Tumor Immunology & Immunotherapy. With strong leadership and institutional commitment, RPCI will continue to focus on recruiting talented investigators to further expand research efforts targeting areas in genetics, investigational imaging and cancer health disparities.